This is a revised application for a competitive renewal of an investigation of behavioral/biochemical correlates in a common disease of aging, Parkinson's disease. This disorder affects nearly one and a half million persons in the North America. It is typically characterized by motor manifestations, but dementia and depression occur commonly in the illness. Prior studies by the current applicants have implicated a reduction in brain serotonin in association with depression in patients with Parkinson's disease. Furthermore, "bradyphrenia", a form of intellectual impairment in this condition may be related to increase turnover of norepinephrine. In the current revised proposal we wish to expand our investigations by examining a putative peripheral maker of central nervous system serotonin, 3H-Imipramine binding capacity in platelets. Moreover, we will examine the relationship between the cerebrospinal fluid metabolite of serotonin: 5-HIAA, plasma 3H-Imipramine binding and depression. We will also begin a parallel design, placebo-controlled investigation of the precursor to serotonin, L-5-hydroxy tryptophan. We will also begin a parallel design, placebo-controlled, investigation of clonidine in patients with bradyphrenia as we have defined this clinical entity. We believe that this investigation will continue to critically examine and confirm behavioral/biochemical correlates in Parkinson's Disease. It will also foster our studies of the aging nervous system.